The oxygen intermediates, superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH ), which are produced by activated neutrophils are known to be important in killing many pathogenic microorganism including aerobic bacteria, fungi, and some parasites. The critical nature of this metabolic response becomes clear from the frequency and severity of infections that occur when these oxygen intermediates are not produced such as in chronic granulomatous disease of childhood (CGD). The oxygen intermediates, on the other hand, may be secreted from activated neutrophils and cause injury to normal host tissue. This constitutes part of the inflammatory response and may lead to some highly undesirable complications of infection such as the adult respiratory distress syndrome (ARDS) which may follow gram negative septicemia and other conditions. A clearer picture of the mechanism of neutrophil activation is important in understanding the role of neutrophils in host-defense and inflammation, and this knowledge should make it possible to modify the process for the benefit of the patient. The objective of this investigation is to determine whether intrinsic change in the plasma membranes of activated neutrophils is alone responsible for the increased oxidation of NAD(P)H and the production of superoxide (O2-), or if fusion or interaction with neutrophil granules is required in this process. Two general approaches will be used in dealing with the problem: (1) One method will be to first expose neutrophils to a particulate stimulant and then separately isolate plasma membrane vesicles that have had contact with the stimulant from those that have not had direct contact. These isolated plasma membrane vesicles will be compared with each other and with plasma membrane vesicles from unstimulated neutrophils for NAD(P)H oxidase activity, (O2-) production, and the presence of certain marker substances and physical characteristics that suggest fusion with granule membranes. (2) Isolated neutrophil plasma membrane vesicles, neutrophil granules and granule membranes, all from unstimulated neutrophils, will be mixed in a variety of combinations and under varying physical and chemical conditions to determine whether in vitro membrane fusion and/or NAD(P)H oxidation can be induced.